The overall aim of this research is to develop a micro-amperometric, minimally invasive, self-compensating, biosensor to continuously monitor blood glucose levels of diabetic patients, with specific attention to monitoring hypoglycemia. One of the primary limitations in many current Continuous Glucose Monitoring System sensors is their susceptibility to biofouling and encapsulation, which causes interference, drift and inaccuracies in reported blood glucose levels. The proposed glucose biosensor consists of a small diameter precious metal wire with a thin film of glucose oxidase immobilized on its surface, and a diffusion limiting, biocompatible membrane overcoat. This sensor will have a rapid and linear response over a wide dynamic range, be stable, readily replaced by a lay user, and will have a low cost disposable sensor element. Under Phase I the sensor configuration will be optimized and a linear response at concentrations up to 400 mg/dL in buffer solution, serum, and stability for at least 24 hours, sensor output repeatability, and the ability to inherently compensate for the effects of biofouling and encapsulation will be demonstrated. The major innovations present in this proposed development include the self-compensation feature; the use of a multilayer membrane structure to reduce interference; and the use of biocompatible diffusion limiting coatings to minimize biofouling and sensor encapsulation. Preliminary testing conducted under internal funding has shown preliminary sensor feasibility in buffer solution. Once the sensor configuration has been optimized and met the Phase I demonstration criteria, more detailed Phase II development and testing are planned.